exam 2 Flashcards
HIV 1 and HIV2 and AIDS
different retroviruses thaat cause AIDS
HIV2 is a milder less virulent version of HIV1 and is limited to west africa
AIDS is acquired immunodeficiency syndrome- when the CD4 count is about 20% less than normal or an unusual infection occurs in a patient otherwise not known to be susceptible, ex: pneumocystis pneumonia
why can we not achieve a future without HIV/AIDS?
probs not possible for a long time
-about 37 million peopole are living with HIV worldwide
with greater than 2 million new infections/year
1.2 million AIDS deaths/year
and effective preventative vaccine still decades away
HIV/AIDS in US
greater than 1.1 million people living with HIV
and people of color are over-represented
there are about 50,000 new infections per year and there is no decline
half of the new infections occur in people under 25
and the majority are men who have sex with men (MSM)
women are getting increasingly infected too
13% of people are infected but unaware
challenges in global HIV care
almost 37 million people are HIV positive, half of those have been diagnosed, 40% are on ART and 32% are on viral suppressors -reasons for this include: lack of health insurance lack of social support competing child care responsibilities food insecurity unstable housing lack of transportation lower education level poverty unemployment, homelessness, mental health or substance abuse probles, racism, stigma, homophoboa, distrust of health care system and providerd
HIV lifecycle
virus binds and enters cell- it is an RNA virus, gets replicated into DNA in the cell
turns into a Provirus which is a circular structure
the provirus is then integrated into the host DNA via integrase and replicates, is transcribes, translated and then more virus particles are assembled and leave the cell. they mature outside the cell and infect other cells
targets of HIV ARV therapty
ARV= drugs that target HIV
The drugs do not kill or cure the virus. However, when taken in combination they can prevent the growth of the virus
Targets include:
- fusion/entry inhibitor
- RNA and reverse transcription inhibitor
- Protease inhibitor
- integrase inhibitor
HIV reservoir cells
they have some cancer like characteristics
-they appear to have an average half-life of 4 years, shorter than some CD4T cells but longer than cells infected by many viruses
integration is random but certain “jackpot” integration sites lead to multi-lineage clones
HIV and 3 month diagnosis
persons linked to care within 3 months of HIV experienced shorter times to viral suppression= higher rate of viral suppression per unit time, verus those that did not
HIV RNA and transmission
viral load predicts transmission
there is no viral transmission if there are less than 1500 cps/ml
PrEP
pre-exposure prophylaxis, or PrEP, is a way for people who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking a pill every day.
a fixed does of tenofovir/emtricitabine is the recommended PrEP regimen for MSM, heterosexually active men and women and IDU (intravenous drug users) who meet the PrEP prescribing criteria
-dose is a single pill taken once daily
Worrisome projections of PrEP continuum of care
of the sexually active MSM, half are aware/willing to take PrEP, less have access of healthcare, even less are likely to receive RX and even less adhere and are effectively protected to achieve HIV protection
HIV combo prevention model
taking ART, PrEP strategies together
3 success stories- ART coverage increased in Cambodia, Malawi and South Africa
HIV and the world
- more people in the world need ART for HIV than is available
- HIV infeciton is deeply entreched in the world and we will not be HIV free even if we get a vaccine for generations
- therapy can prevent new infections (PrEP) and blunt the immune disregulation and consequences of HIV and thus prevent AIDS but delivering therapy to 10s of millions for a lifetime will be very hard
why do microbes partner with higher organisms
microbes are small, have short generation times, large population sizes, propensity for horizontal gene transfer and are metabolically versatile.
multicellular organisms are large, have long generation times, small population sizes, no propensity for lateral gene transfer and are metabolically limited.
By partnering together, they increase one another’s scope
-eukaryotes have limited electron acceptors and donors
while bacteria have a lot and can perform anaerobic resp, chemolithotrophy, methane oxidation and more
our gut microbiome contains 150 times more genes than our own genome therefore supplementing our own functional capacity with an enormous additional potential
human microbiota effect on host biology
-has a huge effect on host
improves immune system, blood circulation, digestion, neural behavior, other systems and tissues such as kidney and bones
-obesity is determined partly by the composition of our microbiome
pathogenesis
imbalance of the ecosystem (microbiota) forces causing imbalance: -intrinsic: genetic -extrinsic: abiotic- antibiotics, pollutants, biotic-invasive species
dysbiosis in microbiome is associated with diseases including inflammatory bowel disease, diabetes, allergies, asthma etc
Clostridium difficile
Anaerobic, gram-positive, sporulating bacterium
A normal(ly inhibited) member of the human gut microbiome
Proliferates after antibiotic therapy, causing disease
Major nosocomial infection
high microbial diversity is associated with health and stability
lack of diversity is apparent in gut microbiome in diseases ranging from obesity to inflammatory bowel disease, diabetes. antibiotics cause drastic reduction in diversity of microbiome with highly variable recovery dynamics, potentially weakening the community’s ability to exclude pathogens
the hygiene hypothesis
Originally: Antimicrobial therapies and increased levels of hygiene reduced the number of infections we acquire and the diversity of our microbial consortium. Thus, we are more susceptible to inflammatory diseases and allergies.
the old friends hypothesis
Now: Early and regular exposure to harmless microorganisms—“old friends” present throughout human evolution and recognized by the human immune system—train the immune system to react appropriately to threats.
inflammatory diseases
diseases that are characterized by inflammation, often involving an abnormal immune response
may have no known cause
ex:
astham, inflammatory bowel disease
arthritis
certain cancers
probiotics
practice of treating patients with live organisms/organismal products to prevent or cure disease symptomes
beneficial function of probiotic bacteria are mostly indirect, and include modulation of the immune system, enhancement of the intestinal epithelial barrier, or competition with pathogens for nutrients
Some probiotic strains produce bacteriocin proteins, which can kill phylogenetically related pathogenic bacteria, and it has been shown that a bacteriocin-producingEscherichia colistrain inhibits colonization by related pathogenic bacteria in the inflamed gut of mice.”
conclusion:
1. immunomodulation
2. altering the consortium in a particular location
3. displacing perturbing species
virus
a foreign nucleic acid that must infect cells to propagate, once the cell is infected the virus hijacks varying amounts of cellular machinery to copy itself, often this means upregulated nucleic acid synthesis in a way that the cells themselves might grow
- retroviruses enter and exit the human genome
- only cause cancer in very specific situations
DNA viruses
RNA viruses
retroviruses
DNA: viruses encoded by DNA like HPV. most DON’T insert into the host genome but a few can such as Hep B virus
RNA: viruses encoded by RNA rather than DNA, ex: influenza, Hep C. most viruses are RNA, sometimes called riboviruses. even though riboviruses never integrate they can cause cancer through other mechanisms
retrovirus: viral particle that has RNA in it, but is “reverse transcribes” to DNA. this DNA can integrate
liver cancer
one of most common and deadly cancers worldwide
is generally caused by at least one and frequently 2 injuries to the liver in a single patient
about 50% caused by HepC
so Hep C is most common cause of liver cancer in US
heptacellular carconoma (liver cancer) hep B is leading cause of this worldwide Hep B is second only ot tobacco in causing the most cancer deaths worldwide
summary: both Hep C and Hep B put people at risk for liver cancer
most people have ongoing inflammation for decades before they get liver cancer
amount of EtOH or amount of Hep B correlates with the magnitude of risk for liver cancer, with HCV the length of time infection present or degree of fibrosis is more important
Hep C virus
alcohol consumption speeds up chronic infection
- only 15-30% of people can resolve Hep C
- host genetic factors also associated with inability to clear hep C virus or response to treatment
HPV and cancer
is very common
causes cervical cancer and other cancers
need to get vaccinated to prevent cancer
HPV is ONLY cause of cervical cancer- so can be eradicated, ex; Australia is making efforts to do so
and also causes head, neck, penile and anal cancer0 all cases where epithelial cells are exposed and potentially persistently infected with HPV
most oropharyngeal cancer is HPV related and men are 4x more likely than women to develop it
people with HIV now more likely to die of cancer than from HIV related opportunistic infections- but still more likely to die than non-people living with HIV
HIV hides in cells in a “cancer like” way
Burkit’s lymphoma
- caused after years of malarial antigen exposure
1. infection with Epstein Barr virus yeilds B-cell proliferation
2. chronic stimulation of antibody producing B cells by malaria
3. activation of a proto-oncogene
4. turn-off of EBV’s transforming genes (not all)
5. mutations in tumor suppressor genes-oncogene
epstein-barr virus
-must provide proliferating -cells a selective advantage to be retained in them as a plasmid replicon
in EBV-positive cancers, most/all tumor cells retain EBV, thus EBV causes these cancers by providing them one or more selective advantages
- EBV can provide at least 2 selective advantages to sustain Burkitt’s lymphomas; it can both inhibit apoptosis and foster proliferation
- 90-95% of humans worldwide are infected with EBV life-long
public health
The art and science of preventing disease and disability, prolonging life, promoting health of populations, and ensuring a healthful environment through organized community effort -more reactive than preventive lately -should mostly focus on prevention, vaccines are classic measure for this
vaccine
a preparation of killed, weakened, or fully infectious microbes or their products given to produce or increase immunity to a particular disease
various categories
vaccines: protect individuals from disease and protect the community by contributing to herd immunity
-active immunity
-immunity and immunologic memory similar to natural infection but without risk of disease
-immunity to most infectious disease agents based on protective antibodies
immunization
process in which the human immune system is prepared against attack by an infectious microorganism
active: natural vs artificial (vaccine)
passive- pre-made antibodies inserted into body
Various categories of vaccine
live attentuated: weakened form of wild virus or bacterium
must replicate to be effective
immune response similar to natural infection
usually effective with one dose
killed vaccine: can’t replicate, generally not as effective as live vaccines
less interference from circulating antibody than live vaccines
-generally need 3-5 doses
immune response mostly humoral
antibody titer may diminish with time
newer technologies: subunit vaccines, conjugate vaccines (enhance immune response against relevant antigen), DNA vaccine, recombinant vector vaccines, nanotechnology
herd immunity
if enough people get vaccinated/were previously infected, it will protect those that weren’t
in highly immunized pop, the few remaining susceptible are protected by the herd
-imp for the protection of those who can’t be vaccinated: the very young, immunocompromised
criteria for vaccine success
containment
elimination
eradication
